Brine residues and organics in the Urvara basin on Ceres.

Ceres is a partially differentiated dwarf planet, as confirmed by NASA's Dawn mission. The Urvara basin (diameter ~170 km) is its third-largest impact feature, enabling insights into the cerean crust. Urvara's geology and mineralogy suggest a potential brine layer at the crust-mantle transition.

Prospective study of the natural history of chronic acid sphingomyelinase deficiency in children and adults: eleven years of observation.

Background: Acid sphingomyelinase deficiency (ASMD) (also known as Niemann-Pick disease types A and B) is a rare and debilitating lysosomal storage disorder. This prospective, multi-center, multinational longitudinal study aimed to characterize the clinical features of chronic forms of ASMD and disease burden over time in children and adults.

Results: Fifty-nine patients (31 males/28 females) ranging in age from 7 to 64 years with chronic ASMD types A/B and B and at least two disease symptoms participated from 5 countries.

One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency.

Purpose: To assess olipudase alfa enzyme replacement therapy for non-central nervous system manifestations of acid sphingomyelinase deficiency (ASMD) in children.

Methods: This phase 1/2, international, multicenter, open-label trial (ASCEND-Peds/NCT02292654) administered intravenous olipudase alfa every 2 weeks with intrapatient dose escalation to 3 mg/kg. Primary outcome was safety through week 64.

A comprehensive monocentric ophthalmic study with Gaucher disease type 3 patients: vitreoretinal lesions, retinal atrophy and characterization of abnormal saccades.

Background: The differentiation between Gaucher disease type 3 (GD3) and type 1 is challenging because pathognomonic neurologic symptoms may be subtle and develop at late stages. The ophthalmologist plays a crucial role in identifying the typical impairment of horizontal saccadic eye movements, followed by vertical ones. Little is known about further ocular involvement.

Safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of the novel enzyme replacement therapy avalglucosidase alfa (neoGAA) in treatment-naïve and alglucosidase alfa-treated patients with late-onset Pompe disease: A phase 1, open-label, multicenter, multinational, ascending dose study.

This multicenter/multinational, open-label, ascending-dose study (NCT01898364) evaluated safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of repeat-dose avalglucosidase alfa (neoGAA), a second-generation, recombinant acid α-glucosidase replacement therapy, in late-onset Pompe disease (LOPD). Patients ≥18 years, alglucosidase alfa naïve (Naïve) or previously receiving alglucosidase alfa for ≥9 months (Switch), with baseline FVC ≥50% predicted and independently ambulatory, received every-other-week avalglucosidase alfa 5, 10, or 20 mg/kg over 24 weeks. 9/10 Naïve and 12/14 Switch patients completed the study.

Long-term outcomes of systemic therapies for Hurler syndrome: an international multicenter comparison.

Purpose: Early treatment is critical for mucopolysaccharidosis type I (MPS I), justifying its incorporation into newborn screening. Enzyme replacement therapy (ERT) treats MPS I, yet presumptions that ERT cannot penetrate the blood-brain barrier (BBB) support recommendations that hematopoietic cell transplantation (HCT) treat the severe, neurodegenerative form (Hurler syndrome). Ethics precludes randomized comparison of ERT with HCT, but insight into this comparison is presented with an international cohort of patients with Hurler syndrome who received long-term ERT from a young age.

Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa.

Background: This post hoc subanalysis examined outcomes in adult patients with Morquio A (mucopolysaccharidosis IVA) who received enzyme replacement therapy (ERT) with elosulfase alfa over a 120-weeks period. Patients ≥18 years of age evaluated in an open-label, long-term extension study of elosulfase alfa (modified per protocol [MPP], n = 32; intent-to-treat [ITT], n = 37; MOR-005; NCT01415427) were compared with the ≥18-year-old untreated population with 2-years follow-up from a Morquio A natural history study (n = 10; MorCAP; NCT00787995). The MOR-005 MPP population excluded patients who underwent orthopedic surgical procedures or were noncompliant with study protocol (defined as missing ≥20% of ERT infusions).

Cause of death in patients with chronic visceral and chronic neurovisceral acid sphingomyelinase deficiency (Niemann-Pick disease type B and B variant): Literature review and report of new cases.

Background: Acid sphingomyelinase deficiency (ASMD), [Niemann-Pick Disease Types A and B (NPD A and B)], is an inherited metabolic disorder resulting from deficiency of the lysosomal enzyme acid sphingomyelinase. Accumulation of sphingomyelin in hepatocytes, reticuloendothelial cells, and in some cases neurons, results in a progressive multisystem disease that encompasses a broad clinical spectrum of neurological and visceral involvement, including: infantile neurovisceral ASMD (NPD A) that is uniformly fatal by 3years of age; chronic neurovisceral ASMD (intermediate NPD A/B; NPD B variant) that has later symptom onset and slower neurological and visceral disease progression; and chronic visceral ASMD (NPD B) that lacks neurological symptoms but has significant disease-related morbidities in multiple organ systems. The purpose of this study was to characterize disease-related morbidities and causes of death in patients with the chronic visceral and chronic neurovisceral forms of ASMD.

Sublimation in bright spots on (1) Ceres.

The dwarf planet (1) Ceres, the largest object in the main asteroid belt with a mean diameter of about 950 kilometres, is located at a mean distance from the Sun of about 2.8 astronomical units (one astronomical unit is the Earth-Sun distance). Thermal evolution models suggest that it is a differentiated body with potential geological activity.

Evaluation of Bone Marrow Infiltration in Non-Neuropathic Gaucher Disease Patients with Use of Whole-Body MRI--A Retrospective Data Analysis.

Purpose: To evaluate whole-body magnetic resonance imaging (WB-MRI) for the assessment of bone marrow infiltration in patients with confirmed Gaucher disease type 1 under long-term enzyme replacement therapy (ERT).

Materials And Methods: This retrospective data analysis included 38 patients in two subgroups. Group A: 10 females, 9 males, 15-29 years, mean age 22 years and Group B: 11 females, 8 males, 29-77 years, mean age 49 years, all treated with alglucerase or imiglucerase for at least 12.

Longitudinal analysis of endurance and respiratory function from a natural history study of Morquio A syndrome.

Objectives: Baseline data from the Morquio A Clinical Assessment Program (MorCAP) revealed that individuals with Morquio A syndrome show substantial impairment in multiple domains including endurance and respiratory function (Harmatz et al., Mol Genet Metab, 2013). Here, 1- and 2-year longitudinal endurance and respiratory function data are presented.

The Morquio A Clinical Assessment Program: baseline results illustrating progressive, multisystemic clinical impairments in Morquio A subjects.

Objectives: The objectives of this study are to quantify endurance and respiratory function and better characterize spectrum of symptoms and biochemical abnormalities in mucopolysaccharidosis IVA subjects.

Methods: MorCAP was a multicenter, multinational, cross sectional study amended to be longitudinal in 2011. Each study visit required collection of medical history, clinical assessments, and keratan sulfate (KS) levels.

The cognitive profile of type 1 Gaucher disease patients.

Background: The absence of neurological symptoms and signs is traditionally considered mandatory for a diagnosis of type 1 Gaucher disease (GD1), but in recent years many reports have emerged on neurological manifestations in GD1 patients. Nevertheless, it has been unclear whether cognitive deficits are part of the disease as well.

Methods: Cognitive function was assessed in a large cohort of GD1 patients with the use of the CDR system, a set of computerised cognitive tests.

Sexual size dimorphism predicts rates of sequence evolution of SPerm Adhesion Molecule 1 (SPAM1, also PH-20) in monkeys, but not in hominoids (apes including humans).

Based on a dataset comprising coding DNA sequences of 23 anthropoid primates, we herein investigate if rates of sequence evolution of SPerm Adhesion Molecule1 (SPAM1, also PH-20), which participates in sperm-egg interaction, is lower in more sexually dimorphic species. For comparison, we analyze sequence evolution of apolipoproteinA-IV (APOA4) and apolipoprotein A-V (APOA5), which should evolve under less or even no sexual selection given their expression in blood, digestive tract, liver, and lungs. Regression analyses provides significant support for a negative dependence of SPAM1 derived branch-specific ratios of non-synonymous to synonymous substitution rates (dN/dS) on sexual size dimorphism (SSD) in a subsample comprising New World and Old World monkeys.

Expanding the clinical spectrum of late-onset Pompe disease: dilated arteriopathy involving the thoracic aorta, a novel vascular phenotype uncovered.

Purpose: Cerebro-vascular arteriopathy has been reported in late-onset Pompe disease (LOPD). Evidence of increased aortic stiffness in some patients and smooth muscle involvement in LOPD raises the possibility of aortic involvement. Our aim was to determine if aortic arteriopathy may be a complication of LOPD.

Photoproduction of eta-mesic 3He.

The photoproduction of eta-mesic 3He has been investigated using the TAPS calorimeter at the Mainz Microtron accelerator facility MAMI. The total inclusive cross section for the reaction gamma3He-->etaX has been measured for photon energies from threshold to 820 MeV. The total and angular differential coherent eta cross sections have been extracted up to energies of 745 MeV.

The reaction gammap-->pi0gamma'p and the magnetic dipole moment of the Delta+ 1232 resonance.

The reaction gammap-->pi(0)gamma'p has been measured with the TAPS calorimeter at the Mainz Microtron accelerator facility MAMI for energies between sqrt[s]=1221-1331 MeV. The cross section's differential in angle and energy have been determined for the photon gamma' in three bins of the excitation energy. This reaction channel provides access to the magnetic dipole moment of the Delta(+)(1232) resonance and, for the first time, a value of mu(Delta(+))=[2.

In-medium modifications of the pipi interaction in photon-induced reactions.

Differential cross sections of the reactions (gamma,pi(0)pi(0)) and (gamma,pi(0)pi(+/-)) have been measured for several nuclei (1H,12C, and (nat)Pb) at an incident-photon energy of E(gamma)=400-460 MeV at the tagged-photon facility at MAMI-B using the TAPS spectrometer. A significant nuclear-mass dependence of the pipi invariant-mass distribution is found in the pi(0)pi(0) channel. This dependence is not observed in the pi(0)pi(+/-) channel and is consistent with an in-medium modification of the pipi interaction in the I=J=0 channel.

Apoplastic pH and Fe(3+) reduction in intact sunflower leaves.

It has been hypothesized that under NO(3)(-) nutrition a high apoplastic pH in leaves depresses Fe(3+) reductase activity and thus the subsequent Fe(2+) transport across the plasmalemma, inducing Fe chlorosis. The apoplastic pH in young green leaves of sunflower (Helianthus annuus L.) was measured by fluorescence ratio after xylem sap infiltration.

Effects of NH(4)(+), NO(3)(-) and HCO(3)(-) on apoplast pH in the outer cortex of root zones of maize, as measured by the fluorescence ratio of fluorescein boronic acid.

A fluorimetric ratio technique was elaborated to measure apoplastic pH in the outer root cortex of maize (Zea mays L.) grown hydroponically. A newly synthesized fluorescent probe, fluorescein boronic acid (pK(a) = 5.

The effects of patellar taping on stride characteristics and joint motion in subjects with patellofemoral pain.

Although patellar taping has been reported to be effective in reducing pain, the effects of this procedure on functional outcomes, such as ambulation, have not been documented. The purpose of this study was to compare stride characteristics and joint motion in subjects with patellofemoral pain, with and without the application of patellar taping using the McConnell technique. Fifteen female subjects between the ages of 14 and 41 years with diagnosis of patellofemoral pain participated in this study.

In vivo effects of fluconazole on lymphocyte subpopulations of the thymus and spleen in mice: flow cytometry analysis.

Fluconazole is a triazole compound developed for the therapy of fungal infections, especially for systemic fungal infections. In this study 2.5 and 5.